Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 111, Issue 32, Pages 11792-11797Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1404671111
Keywords
immunological memory; antibody production
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Funding
- Ministry of Education, Culture, Sports, Science, and Technology
- Japan Science and Technology Agency, Core Research for Evolutionary Science and Technology
- Grants-in-Aid for Scientific Research [22113006, 25293115] Funding Source: KAKEN
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In primary humoral responses, B-cell lymphoma 6 (Bcl6) is a master regulator of follicular helper T (T-FH) cell differentiation; however, its activation mechanisms and role in memory responses remain unclear. Here we demonstrate that survival of CXCR5(+) T-FH memory cells, and thus subsequent recall antibody response, require Bcl6 expression. Furthermore, we show that, upon rechallenge with soluble antigen Bcl6 in memory T-FH cells is rapidly induced in a dendritic cell-independent manner and that peptide: class II complexes (pMHC) on cognate memory B cells significantly contribute to this induction. Given the previous evidence that antigen-specific B cells residing in the follicles acquire antigens within minutes of injection, our results suggest that memory B cells present antigens to the cognate T-FH memory cells, thereby contributing to rapid Bcl6 reexpression and differentiation of the T-FH memory cells during humoral memory responses.
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